[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › Neurotransmission in the central nervous system # Neurotransmission in the central nervous system How brain cells talk through chemical messengers, and how sedatives, antidepressants, antipsychotics and other CNS drugs change that conversation. Updated Nov 2, 2026 Almost every drug that acts on the brain works at the synapse: it changes how a transmitter is made, stored, released, detected or removed. Knowing the main transmitter systems (glutamate, GABA, the monoamines, acetylcholine and the neuropeptides) makes the effects and side effects of CNS drugs predictable. ## Key points - Glutamate is the main fast excitatory transmitter; GABA (and glycine in the spinal cord and brainstem) are the main fast inhibitory transmitters. - Ionotropic receptors are ion channels that open in milliseconds; metabotropic receptors act through G proteins and second messengers, more slowly and for longer. - Dopamine, noradrenaline, serotonin and acetylcholine come from small nuclei but project widely, so they tune mood, attention, movement, sleep and reward. - Drugs act at every step: synthesis, vesicle storage, release, receptors, reuptake and enzymatic breakdown. - A side effect is often the same mechanism acting in a different pathway (for example, dopamine blockade that helps psychosis but causes parkinsonism). ## The synapse, step by step An action potential opens calcium channels in the nerve terminal; calcium triggers vesicles to fuse and release transmitter into the cleft. The transmitter binds receptors on the next cell and is then cleared: amino acids and monoamines by reuptake transporters, acetylcholine by acetylcholinesterase, neuropeptides by peptidases. Clearing keeps each signal brief. - Synthesis: levodopa is the precursor that the brain turns into dopamine - Storage: VMAT2 inhibitors (tetrabenazine) empty monoamine vesicles - Reuptake: SSRIs block the serotonin transporter - Breakdown: cholinesterase inhibitors (donepezil) and MAO inhibitors slow removal ## Excitation and inhibition: glutamate and GABA Glutamate acts on ionotropic AMPA, NMDA and kainate receptors and on metabotropic receptors. NMDA antagonists such as ketamine (anaesthesia) and memantine (dementia) dampen it. GABA-A receptors are chloride channels: benzodiazepines and z-drugs make GABA more effective at its own site, barbiturates also hold the channel open, which is why they are more dangerous in overdose. Many antiseizure medicines tip the balance toward inhibition or reduce glutamate release. - Benzodiazepines need GABA to work; flumazenil reverses them at the same receptor - Gabapentinoids bind a calcium-channel subunit and reduce transmitter release - Mixing CNS depressants (alcohol, opioids, benzodiazepines) adds up, with risk of breathing depression ## The monoamines and acetylcholine Dopamine pathways handle movement (nigrostriatal), reward (mesolimbic) and prolactin control (tuberoinfundibular). Noradrenaline from the locus coeruleus sets arousal; serotonin from the raphe nuclei touches mood, sleep, appetite and nausea. Acetylcholine in the basal forebrain supports memory, which is why anticholinergic drugs can cause confusion in older adults. Antidepressants raise monoamine signalling; antipsychotics block dopamine D2 receptors (see serotonin and dopamine pharmacology). ## Neuropeptides and other messengers Peptides such as endorphins, enkephalins, substance P and orexin are often released together with a classic transmitter and act slowly on G protein-coupled receptors. Opioids mimic the endogenous opioid peptides; NK1 antagonists (aprepitant) block substance P in the vomiting centre; orexin antagonists promote sleep. Endocannabinoids, nitric oxide and ATP are further signals that drugs can target. ## Thinking like a pharmacologist For any CNS drug, ask three questions: which transmitter, which receptor, which pathway. The answer predicts both the wanted effect and the typical adverse effects. Combining two drugs that raise serotonin, for example, can cause serotonin syndrome, with agitation, tremor, fever and muscle rigidity. ## Memory aid «Glu goes, GABA slows»: glutamate is the accelerator, GABA the brake; most CNS drugs press one pedal or the other. ## Test yourself Think of the answer, then tap the question to see it. ## Why are benzodiazepines safer in overdose than barbiturates when taken alone? Benzodiazepines only increase the effect of GABA that is already present at the GABA-A receptor, while barbiturates can also open the chloride channel directly, so their effect has no ceiling. ## Which receptor do ketamine and memantine block? The NMDA type of glutamate receptor. ## How do metabotropic receptors differ from ionotropic receptors? Ionotropic receptors are ion channels that open in milliseconds; metabotropic receptors act through G proteins and second messengers, so their effects are slower and last longer. ## Why can an antipsychotic cause parkinsonism? It blocks dopamine D2 receptors in all dopamine pathways, including the nigrostriatal pathway that controls movement. [Add to my cards (4)](https://durgical.app/estudiar/?add=/en/pharmacology/topics/neurotransmission-in-the-central-nervous-system/) [More Pharmacology questions →](https://durgical.com/en/practice/?f=pharmacology) ## Example drugs - [Diazepam](https://durgical.com/en/pharmacology/diazepam/) - [Zolpidem](https://durgical.com/en/pharmacology/zolpidem/) - [Valproic acid](https://durgical.com/en/pharmacology/valproic-acid/) - [Memantine](https://durgical.com/en/pharmacology/memantine/) - [Ketamine](https://durgical.com/en/pharmacology/ketamine/) - [Fluoxetine](https://durgical.com/en/pharmacology/fluoxetine/) - [Haloperidol](https://durgical.com/en/pharmacology/haloperidol/) - [Morphine](https://durgical.com/en/pharmacology/morphine/) - [Flumazenil](https://durgical.com/en/pharmacology/flumazenil/) - [Donepezil](https://durgical.com/en/pharmacology/donepezil/) ## Connections ## Related classes 9 - [Benzodiazepines](https://durgical.com/en/pharmacology/classes/benzodiazepines/) - [Z-drug hypnotics](https://durgical.com/en/pharmacology/classes/z-drug-hypnotics/) - [Antiseizure medicines](https://durgical.com/en/pharmacology/classes/antiseizure-medicines/) - [Gabapentinoids](https://durgical.com/en/pharmacology/classes/gabapentinoids/) - [NMDA receptor antagonists (anti-dementia)](https://durgical.com/en/pharmacology/classes/nmda-receptor-antagonists/) - [Selective serotonin reuptake inhibitors (SSRIs)](https://durgical.com/en/pharmacology/classes/selective-serotonin-reuptake-inhibitors/) - [First-generation antipsychotics](https://durgical.com/en/pharmacology/classes/first-generation-antipsychotics/) - [Opioids and antagonists](https://durgical.com/en/pharmacology/classes/opioids-and-antagonists/) - [Cholinesterase inhibitors](https://durgical.com/en/pharmacology/classes/cholinesterase-inhibitors/) [← All of pharmacology](https://durgical.com/en/pharmacology/) Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given. Sources: [Serotonin syndrome: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/007272.htm) (MedlinePlus (U.S. National Library of Medicine), 2026). ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/pharmacology/topics/neurotransmission-in-the-central-nervous-system/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/topics/neurotransmission-in-the-central-nervous-system/